Glaucoma, which some estimate affects 2 million adults over 40, is an impairment of vision caused by too much fluid pressure within the eye.
Surgical treatment for glaucoma is effective; however, it is expensive, and some surgeons will use surgery only as a last resort.
Glaucoma stems from an excess of fluid behind the cornea, the three-layered tissue that acts as a window to let light enter. Fluid-carrying nutrients, such as potassium and glucose, constantly wash the inside of the cornea to keep it healthy, much as tears wash the outside of the cornea.
In some middle-aged adults, fluids build up faster than can be absorbed back into the blood for one of two reasons: the ciliary body (a tiny tissue behind the iris) may excrete too much fluid, or the fluid may not drain off at the normal rate.
Either way, the excess fluid damages the optic nerve. At first a glaucoma victim usually experiences a subtle loss of peripheral vision--objects will seem to disappear from certain spots to the side. But glaucoma often leads to middle-age blindness.
Unfortunately, the two approaches to general drug usage in treating glaucoma--topical (dropped into the eye) and oral (through the mouth)--each have a peculiar set of side effects.
To make the long journey, oral drugs must be dosed in very high concentration. One class of drugs, called carbonic anhydrase inhibitors, slow the formation of fluid by inhibiting a chemical reaction at the ciliary body. Along with their well-tested effectiveness comes nausea, tingling in fingers and toes, and other side effects. Oral drugs generally do not, however, cause side effects in the eye, but the systemic delivery system is slow and causes other side effects.
From the above discussion it can be seen that there is a continuing need for the development of new drugs that can be applied topically in order to avoid systemic effects, and which may at the same time still be highly effective. This, of course, necessitates that the compound be one which will, first of all, effectively evoke a response which will provide the correct intraocular pressure, and secondly, penetrate the cornea rapidly and distribute well to the active site, i.e. ciliary body of the eye, or perhaps the trabecular meshwork. It goes without saying that compounds which are active as intraocular pressure inhibitors, but have limited penetrability across the cornea and to the site of activity are, as a practical matter, of limited value in developing truly effective topical glaucoma treatments, even though they may have some test activity in vitro, i.e. in a test tube. Put another way, if the compound does not have the correct distribution and penetration properties, its chances of being pharmacologically active, when topically applied to an affected eye in patients, are small at best. Thus, it is important if one is developing effective topical medicaments, that they be active in vitro, and that they be active when actually applied to an affected eye from the standpoint of penetrating the cornea and reaching the active site for effective treatment of glaucoma. There has been some work in the past with ethacrynic acid, but it has not proven effective in human models, even though it may have good pharmacological activity.
Accordingly, it is a primary object of the present invention to provide a new, highly effective topical treatment for glaucoma that has a surprisingly fast rate of absorption in comparison with ethacrynic acid, coupled with a demonstrated lack of toxicity risk and in vivo effectiveness.
It is another objective of the present invention to provide a new composition and new treatment using ethyl ethacrynate for glaucoma that can be used topically to avoid many of the undesirable side effects of other currently available treatments.
The method and manner of accomplishing each of the above objectives, as well as others, will become apparent from the detailed description of the invention which follows hereinafter.